6-Shogaol能通过减轻氧化应激、炎症和凋亡,并激活核呼吸因子-2/血红素氧合酶-1信号通路,保护大鼠免受异丙肾上腺素诱导的心脏损伤。
6-Shogaol protects against isoproterenol-induced cardiac injury in rats through attenutating oxidative stress, inflammation, apoptosis and activating nuclear respiratory factor-2/heme oxygenase-1 signaling pathway.
发表日期:2022 Dec
作者:
H Li, J Shen, Y Zhang, L Hu, W Luo
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
该研究探究了6-Shogaol对异丙肾上腺素盐酸盐(ISO)诱导的心肌损伤的预防作用。在预处理和最后两天(第13和14天)通过皮下注射给予6-Shogaol(50毫克/千克体重)和ISO诱导(85毫克/千克体重)的14天内。 ISO 诱导的大鼠血清中的心脏标志物,如肌酸激酶(CK)、肌酸激酶-MB(CK-MB)、乳酸脱氢酶(LDH)、心脏肌钙蛋白T(cTn T)和I(cTn I)均升高。此外,脂质过氧化标志物如硫代巴比妥酸反应物(TBARS)和脂质过氧化物(LOOH)也升高,超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)和还原型谷胱甘肽(GSH)在ISO处理的心脏组织中的活性/水平降低。此外,在ISO诱导的缺血大鼠中,炎症和核呼吸因子(Nrf)-2信号分子也被上调。6-Shogaol预处理降低了心脏和脂质过氧化标志物的活性,并增强了ISO诱导的心脏损伤大鼠的抗氧化状态。此外,6-Shogaol预处理抑制了血清炎症标志物:肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、核因子-κB(NF-κB)、Nrf-2分子和血红素氧合酶(HO)-1在ISO诱导的心脏损伤大鼠中。我们注意到,6-Shogaol的作用抑制了原癌基因如B细胞淋巴瘤2(Bcl-2)相关的X蛋白(Bax)、Fas、半胱氨酸蛋白酶-3、-8、-9、细胞色素C和炎症基因的表达,并增加了ISO处理大鼠的Bcl-2表达。6-Shogaol在ISO诱导的心肌损伤大鼠中的心脏保护作用可能是由于其减少了氧化应激、炎症和细胞凋亡的能力,可能通过 Nrf-2 / HO-1信号通路。
The current study investigated the preventive effect of 6-Shogaol on isoproterenol hydrochloride (ISO)-induced myocardial cardiac injury. 6-Shogaol (50 mg/kg b.w.) was administered for 14 days at pretreatment and ISO-induction (85 mg/kg b.w.) for the last two days (13th and 14th days) by subcutaneous injection. Cardiac markers in serum like creatine kinase (CK), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), cardiac troponins T (cTn T) and I (cTn I) increased in ISO-induced rats. Moreover, lipid peroxidative markers like thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides (LOOH) were raised, and the activities/level of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) were diminished in ISO-treated heart tissue. In addition, inflammatory and nuclear respiratory factor (Nrf)-2 signalling molecules were upregulated in ISO-induced ischemic rats. 6-Shogaol pretreatment decreased the activities of cardiac and lipid peroxidative markers and enhanced the antioxidant status in ISO-induced cardiac injury rats. Further, 6-Shogaol pretreatment inhibited serum inflammatory markers: tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), nuclear factor-kappaB (NF-κB), Nrf-2 molecule and heme oxygenase (HO)-1 in ISO-induced cardial damage rats. We noticed the effect of 6-Shogaol inhibited pro-apoptotic genes like B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), Fas, caspase-3, -8, -9, cytochrome C, and inflammatory genes and increased Bcl-2 expression in ISO-treated rats. The cardioprotective activity of 6-Shogaol in rats with ISO-induced myocardial damage may be due to its ability to reduce oxidative stress, inflammation, and apoptosis, perhaps via the Nrf-2/HO-1 signalling pathway.